Histological Changes and Immunohistological Analysis of Interstitial Cells of Cajal in Pelvi-Ureteric Junction Obstruction: Correlation With Preoperative Renal Function

TL;DR

This study examines the microscopic changes in the pelvi-ureteric junction of patients with obstruction and finds that reduced interstitial cells of Cajal and increased fibrosis correlate with poor kidney function.

Contribution

The study provides new insights into the histological and immunohistological features of pelvi-ureteric junction obstruction and their correlation with preoperative renal function.

Findings

Histological changes like fibrosis and smooth muscle hypertrophy are more severe at the obstructed pelvi-ureteric junction.

Interstitial cells of Cajal are significantly reduced in obstructed segments and correlate with poor renal function.

Older patients show higher grades of fibrosis at the pelvi-ureteric junction.

Abstract

Introduction: A decrease in smooth muscle cells at the pelvi-ureteric junction (PUJ), along with abnormal muscle orientation, collagen deposition, and a reduction in Cajal cells, is proposed as the primary cause of obstruction at the PUJ. The findings on histology and the density of interstitial cells of Cajal (ICCs) in patients operated for pelvi-ureteric junction obstruction (PUJO) show variable observations. Clinicians often face a dilemma during the diagnosis and management of patients with PUJO. Hence, to address this knowledge gap, a study of the detailed microanatomy of PUJO and the number of ICCs has been undertaken. A correlation of these parameters with preoperative renal function will help clinicians during postoperative follow-up and prediction of the surgical outcome.

Methodology: The study was carried out on resected specimens from all 54 patients who underwent surgery for PUJO during the study period. The gross features were noted, and bits were taken from the obstructed middle part of the PUJ and the normal distal surgical margin (DSM). The sections were stained with routine hematoxylin and eosin (H&E), Masson's trichrome for collagen, and immunohistochemistry using the c-Kit antigen for ICCs.

Results: The study showed a male preponderance of PUJO and antenatal detection in 36 (66.7%) cases. Histological evaluation on H&E staining revealed a narrowed ureteric lumen, a lining epithelium that was either thickened or normal, hypertrophied smooth muscle, and increased fibrosis, most prominently at the PUJ. In some cases, the wall showed increased vascularity, lymphocytic infiltration, prominent nerve bundles, muscle hypertrophy, and fibrosis. These findings were more marked at the obstructed segment. In a few cases, the wall showed atrophied smooth muscles and severe perifascicular fibrosis, which was more prominent at the PUJ. There was a significant difference in the thickness of the lamina propria and muscle layer at PUJ and DSM in the older age group. Masson's trichrome stain is useful for detecting and grading fibrosis at the PUJ due to its differential staining properties. It showed higher grades of fibrosis in the obstructed segments of PUJ and older patients. The ICCs were reduced in the obstructed segment of PUJ as well as the DSM in a majority of the patients. Few patients had normal ICCs at the PUJ and surgical margins. There was a strong correlation between low renal function on nuclear scan, grade 4 fibrosis on Masson's trichrome stain, and absence of ICCs on c-Kit-stained slides.

Conclusions: On histological examination, the PUJ showed a narrow lumen, severe grades of fibrosis, muscle hypertrophy/atrophy, and low to absent ICCs, which correlate with severe obstruction and reduced renal function. Age is an important factor in the progression of the disease, and significantly higher grades of fibrosis were noted in older patients. Regular follow-up with USG and renal scan for recurrence of obstruction in the early postoperative period is of prime importance.

Figures